A Randomized, Open-label, Parallel-group Study to Determine the Efficacy of Sequential High-intensity Focused Ultrasound (HIFU) Ablation Versus Fixed-dose Radioiodine-131 Therapy in Moderate-sized Non-toxic Multinodular Goiter

Non-toxic multinodular goiter (NMNG) is a condition referred to as a nodular enlargement of the thyroid gland due to the presence of two or more nodules without clinical hyper- or hypothyroidism. It is undoubtedly one of the most common thyroid disorders worldwide and it is estimated that more than 5% of the female population have a clinically-palpable NMNG (1,2). Although the majority of NMNGs do not cause symptoms and therefore, do not require any intervention other than simple surveillance, some can cause local pressure symptoms and cosmetic concerns over time (1-3). For NMNGs that cause symptoms, the most widely-accepted treatment has been surgical resection either in the form of a hemithyroidectomy or total thyroidectomy. Despite being safe when done in experienced hands, surgery is associated with complications such as recurrent laryngeal nerve injury and hypoparathyroidism, both of which can be permanent. In addition, a general anesthesia is almost inevitably required when surgery is performed. As a result, non-surgical thermal ablation techniques have been increasingly recognized as an alternative treatment in symptomatic NMNG (4). These ablation techniques utilize thermal energy to cause shrinkage of adenomatous nodules and thereby, relieve symptoms. Types of ablation include radiofrequency, laser and microwave ablations and more recently, high intensity focused ultrasound (HIFU). Regardless of which ablation technique, they have all been shown to not only induce significant nodule shrinkage but also alleviate symptoms (4-6). Radioactive iodine (131I) therapy (RAIT) is another promising non-surgical alterative which is recommended in patients who refuse or have contraindications for surgery. Despite being a less recognized treatment in both Asia and North America, this treatment has increasingly been adopted. In some European countries such as Denmark and Netherlands, it has replaced surgery as the treatment of choice in moderately-sized NMNG as recommended in recently-published clinical practice guidelines (1,7,8). However, RAIT has limitations. For example, it is less applicable in very large-sized NMNG (>100 mL) because large goiters tend to have a lower radioiodine uptake leading to suboptimal shrinkage. Also considerable inconsistency in goiter shrinkage has been reported (7). With our population getting older and the general public placing a greater emphasis on preserving organ function and lessinvasive treatments, non-surgical treatment alternatives will have an increasing role in the future treatment of NMNG. To our knowledge, it remains unknown whether one particular treatment modality is superior over the other modality because there has not been any direct comparison between the two modalities. Only one previous study compared treatment efficacy between laser ablation and RAIT. However, it mainly focused on the treatment of toxic thyroid nodules (9). To enhance treatment efficacy, a recent study reported promising results of combining the effect of thermal ablation and RAIT (10).